Structural influence on the solid state intermolecular hydrogen bonding of substituted thioureas

Several thiourea derivatives have been found to possess biological activity. In particular, phenethyl thiazolyl thiourea derivatives with a heterocyclic ring exhibit potent antiviral activity. These thiourea derivatives were also found to inhibit RT, the reverse transcriptase enzyme, by binding the non-nucleoside inhibitor site of RT. To better understand the nature of the binding of these compounds a detailed crystal structure analysis on these thiourea compounds was undertaken. Here, we report, the results of our X-ray crystal structure study of substituted thiourea compounds. Comparison of the hydrogen bonding characteristics exhibited by structurally distinct thiourea analogs was informative concerning their inter- and intramolecular hydrogen bonding. Additionally, we found that among the thioureas studied, the 2,5-dimethoxy substituted phenethyl thiourea had strong intramolecular hydrogen bonding forming a nine-member ring in the crystal lattice that was absent in the other methoxy substituted phenethyl thioureas examined. Comparison of the structures demonstrated that the presence of a heterocyclic nitrogen atom in the ring results in the formation of a stable six-member ring rather than a nine-member ring.